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Updated: Mar 8, 2026
Production and Characterization of Human Macrophages from Pluripotent Stem Cells
Published on: April 16, 2020
Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident
Julian Buchrieser1, William James1, Michael D Moore1
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Abstract:
Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs) as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1)-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.
Insights
Human macrophages develop differently based on origin. Tissue-resident macrophages arise from Myb-independent progenitors, while blood monocytes originate from Myb-dependent hematopoietic stem cells.
Area of Science:
- Developmental biology
- Immunology
- Stem cell research
Background:
- Tissue-resident macrophages (e.g., microglia, Kupffer cells) originate from Myb-independent yolk sac progenitors.
- Adult blood monocytes and other infiltrating macrophages derive from Myb-dependent hematopoietic stem cells (HSCs).
- Previous findings in mice lack formal demonstration in human development.
Purpose of the Study:
- To model human hematopoietic development using human induced pluripotent stem cells (iPSCs).
- To investigate the MYB-dependency of human monocyte/macrophage development.
- To determine the developmental relationship of iPSC-derived macrophages to known macrophage populations.
Main Methods:
- Utilized human induced pluripotent stem cells (iPSCs) for hematopoietic development modeling.
- Employed CRISPR-Cas9 gene editing to create MYB knockouts.
- Analyzed the dependency of monocyte/macrophage development on MYB, RUNX1, and SPI1 (PU.1).
Main Results:
- Human iPSC-derived monocytes/macrophages exhibit MYB-independent development.
- Development is dependent on RUNX1 and SPI1 (PU.1) in this model.
- These findings suggest a developmental link to Myb-independent tissue-resident macrophages.
Conclusions:
- Human iPSC-derived macrophages are developmentally related to Myb-independent tissue-resident macrophages.
- Human iPSC-derived macrophages serve as a valid model for studying these cell types.
- This research clarifies distinct developmental pathways for human macrophage populations.
